Stabilization of myelin mRNAs as measured in a brain slice system.
The stabilization and destabilization of myelin mRNA is increasingly recognized as a major control point in regulating myelin gene expression. A brain slice system was developed and characterized to study mRNA stability in actively myelinating oligodendrocytes. The mRNA half-life of a major CNS myelin protein, proteolipid protein (PLP), was measured to be 5 hr. The half-life of another CNS myelin protein mRNA, myelin basic protein (MBP), was measured to be greater than 12 hr. A long half-life for MBP mRNA is consistent with MBP mRNA being stable long enough to be translocated to the myelin internode where it is then translated. Using semi-quantitative reverse transcriptase-PCR, it was determined that there was no differential stabilization between the two major PLP mRNA isoforms, PLP and DM20. It was also determined that protein synthesis was required for the specific stabilization of PLP/DM20 mRNAs. Inasmuch as PLP is a major structural protein of the CNS myelin, the PLP/DM20 mRNAs have relatively short half-lives. However, the PLP/DM20 mRNAs half-lives may be increased by the action of trans-acting factors that are themselves very labile.
Mathisen
P M
PM
Department of Neurosciences, Research Institute, The Cleveland Clinic Foundation, Ohio 44195, USA. mathisp@cesmtp.ccf.org
Johnson
J M
JM
Kawczak
J A
JA
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003609:Dactinomycin / Q000494:pharmacology; D006207:Half-Life; D066298:In Vitro Techniques; D004676:Myelin Basic Protein / Q000378:metabolism; D009185:Myelin Proteins / Q000235:genetics*; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000187:drug effects
D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D003609:Dactinomycin